KEGG   PATHWAY: mlf04620
Entry
mlf04620                    Pathway                                
Name
Toll-like receptor signaling pathway - Myotis lucifugus (little brown bat)
Description
Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK.
Class
Organismal Systems; Immune system
Pathway map
mlf04620  Toll-like receptor signaling pathway
mlf04620

Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102423767  TLR1; toll-like receptor 1 [KO:K05398]
102424442  TLR2; toll-like receptor 2 [KO:K10159]
102424076  TLR6; toll-like receptor 6 [KO:K10169]
102423528  LBP; LOW QUALITY PROTEIN: lipopolysaccharide-binding protein [KO:K05399]
102425384  lipopolysaccharide-binding protein-like [KO:K05399]
102425732  CD14; monocyte differentiation antigen CD14 [KO:K04391]
102433233  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
102430015  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
102437402  TLR4; toll-like receptor 4 [KO:K10160]
102431957  TLR5; LOW QUALITY PROTEIN: toll-like receptor 5 [KO:K10168]
102428265  TLR7; toll-like receptor 7 [KO:K05404]
102427949  TLR8; toll-like receptor 8 [KO:K10170]
102440408  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102431868  TLR9; LOW QUALITY PROTEIN: toll-like receptor 9 [KO:K10161]
102435667  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
102422649  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102441064  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102433534  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102427890  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102441522  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
102429230  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102426106  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102419324  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
102443221  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102439923  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102425374  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
102432819  TIRAP; toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
111824600  FADD; FAS-associated death domain protein [KO:K02373]
102439369  CASP8; LOW QUALITY PROTEIN: caspase-8 [KO:K04398] [EC:3.4.22.61]
102433848  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X3 [KO:K04733] [EC:2.7.11.1]
102418742  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
102436804  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102427825  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
102439412  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102429407  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102436137  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
102425603  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102417312  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4 [KO:K07209] [EC:2.7.11.10]
102422347  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102435748  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102424236  RELA; transcription factor p65 [KO:K04735]
102428565  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
102417411  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
102423748  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102417755  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102422236  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102426303  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
102438357  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102429748  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102438914  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102437934  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102430582  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102418507  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437415  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102417433  FOS; proto-oncogene c-Fos [KO:K04379]
102437558  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102427189  IL1B; interleukin-1 beta [KO:K04519]
102431882  IL6; interleukin-6 [KO:K05405]
102431058  IL12A; interleukin-12 subunit alpha [KO:K05406]
102435627  IL12B; interleukin-12 subunit beta [KO:K05425]
102428495  CXCL8; interleukin-8 [KO:K10030]
102438250  CCL5; C-C motif chemokine 5 [KO:K12499]
102437330  C-C motif chemokine 3-like 1 [KO:K05408]
102437642  C-C motif chemokine 18-like [KO:K05408]
102426459  C-C motif chemokine 4-like [KO:K12964]
102437023  C-C motif chemokine 4 [KO:K12964]
102433809  TIR domain-containing adapter molecule 2 isoform X1 [KO:K05409]
102426981  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102425101  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102425960  IRF5; interferon regulatory factor 5 isoform X1 [KO:K09446]
102417152  SPP1; osteopontin [KO:K06250]
102441851  IKBKE; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102424113  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102420724  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
102422872  IRF3; interferon regulatory factor 3 isoform X2 [KO:K05411]
102439545  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
102417504  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
102436777  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
102417209  IFNB1; interferon beta [KO:K05415]
102427197  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
102419381  IFNAR2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131]
102442353  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
102433832  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102424662  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102430852  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
102425810  IRF9; interferon regulatory factor 9 [KO:K04693]
102427389  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102425201  CXCL9; C-X-C motif chemokine 9 isoform X1 [KO:K05416]
102427083  CXCL11; C-X-C motif chemokine 11 [KO:K12672]
Reference
  Authors
Kawai T, Akira S.
  Title
TLR signaling.
  Journal
Semin Immunol 19:24-32 (2007)
DOI:10.1016/j.smim.2006.12.004
Reference
  Authors
O'Neill LA, Bowie AG.
  Title
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
  Journal
Nat Rev Immunol 7:353-64 (2007)
DOI:10.1038/nri2079
Reference
  Authors
Honda K, Taniguchi T.
  Title
IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.
  Journal
Nat Rev Immunol 6:644-58 (2006)
DOI:10.1038/nri1900
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and Type I interferons.
  Journal
J Biol Chem 282:15319-23 (2007)
DOI:10.1074/jbc.R700009200
Reference
  Authors
Akira S, Uematsu S, Takeuchi O.
  Title
Pathogen recognition and innate immunity.
  Journal
Cell 124:783-801 (2006)
DOI:10.1016/j.cell.2006.02.015
Reference
  Authors
Yamamoto M, Takeda K, Akira S.
  Title
TIR domain-containing adaptors define the specificity of TLR signaling.
  Journal
Mol Immunol 40:861-8 (2004)
DOI:10.1016/j.molimm.2003.10.006
Reference
  Authors
Means TK, Hayashi F, Smith KD, Aderem A, Luster AD.
  Title
The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells.
  Journal
J Immunol 170:5165-75 (2003)
DOI:10.4049/jimmunol.170.10.5165
Reference
  Authors
Aderem A, Smith KD.
  Title
A systems approach to dissecting immunity and inflammation.
  Journal
Semin Immunol 16:55-67 (2004)
DOI:10.1016/j.smim.2003.10.002
Reference
  Authors
Banerjee A, Gerondakis S.
  Title
Coordinating TLR-activated signaling pathways in cells of the immune system.
  Journal
Immunol Cell Biol 85:420-4 (2007)
DOI:10.1038/sj.icb.7100098
Reference
  Authors
Loniewski KJ, Patial S, Parameswaran N.
  Title
Sensitivity of TLR4- and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF-receptor-associated-factor-6 revealed by RNAi in mouse macrophages.
  Journal
Mol Immunol 44:3715-23 (2007)
DOI:10.1016/j.molimm.2007.04.002
Reference
  Authors
Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG.
  Title
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
  Journal
Nat Immunol 1:533-40 (2000)
DOI:10.1038/82797
Reference
  Authors
Uematsu S, Akira S.
  Title
Toll-like receptors and innate immunity.
  Journal
J Mol Med 84:712-25 (2006)
DOI:10.1007/s00109-006-0084-y
Related
pathway
mlf04010  MAPK signaling pathway
mlf04060  Cytokine-cytokine receptor interaction
mlf04064  NF-kappa B signaling pathway
mlf04120  Ubiquitin mediated proteolysis
mlf04151  PI3K-Akt signaling pathway
mlf04210  Apoptosis
mlf04610  Complement and coagulation cascades
mlf04630  JAK-STAT signaling pathway
KO pathway
ko04620   
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